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5-1-1938

Gas gangrene

Harold H. Macumber University of Nebraska Medical Center

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Recommended Citation Macumber, Harold H., "Gas gangrene" (1938). MD Theses. 675. https://digitalcommons.unmc.edu/mdtheses/675

This Thesis is brought to you for free and open access by the Special Collections at DigitalCommons@UNMC. It has been accepted for inclusion in MD Theses by an authorized administrator of DigitalCommons@UNMC. For more information, please contact [email protected]. GAS GANGRENE

:BY

HAROLD H. MACUMBER

•••

SENIOR THESIS

PRESENTED TO THE COLLEGE OF MEDICINE UNIVERSITY OF NEBRASKA

OM.AHA, 1938

" CONTENTS

A INTRODUCTION

:s EARLY HISTORY ...... l c INCIDENCE ...... 6 D ETIOLOGY ••••••••••••••••••••••••••••••••••••••••••••••••••• 10

E PATHOLOGY •••••••••••••••••••••••••••••••••••••••••••••••••• 21

F CLINICAI.. PICTURE ••••••••••••••••••••••••••••••••••••••••••• 28

(1) SYNDROlvlE • • • • • • • • • • • • • • • • • • • . • • • • • • • • • • • • • • • • • • • • • • 2 8

(2) DIAGNOSIS .••••.•••••••••••••••••••••••••••••••••••• 32

G TBJilA.TMENT •••••••••••••••••••••••••••••••••••••••••••••••••• 35

( 1) PROP ml.a.A.XIS •••••••••••••••.••••••••••••••••••••••• 38

(2) SURG:EB.Y . • • • • • • • • • • • • • • . • • • • • • • • • • • • • • • • • • • • • • • • • • • • 40

(3) SERO'l'HERA.PY • • • • • • • • • • • • • • • • • • • • • • • • • •••••••••••••• 41

( 4) BADIATION •••••••••••••••••••.••••••••••••••••••••• 43

(5) OXIDIZING AGENTS •• ~ •..••••••••••••••••.••.•••••••• 45

(6) NON-SPECIFIC ANTISEPTICS •••••••.••••••.••••••••.•• 46

\ H PROGNOSIS ...... • ...... 48

~' ' 480953 INTRODUC!ION Modern surgery has known no greater problem than the successful management of cases of gangrene induced b7 gas-producing bacilli. No other disease that falls to the lot of the surgeon places ao heavy a burden on his Judgement nor is so dependent upon his manage­ ment aa this dread condition. !he history of the literature bearing on this subJeot ia a long one, made up, as is the history of moat diseases, of a vast

DWllber of irrelevant papers, JD8D1' case reports of value in the final 8WJllDation, and a few path-forming papers. That there is no completel7 satisfactory treatment is at once evident b7 the fact that so Jll8Zl1' different methods have been propounded. ~ more authors could have been quoted, but in the main, it would have been Just a repetition of the information alre~ set forth. To keep astride the ever ·cha:aging viewpoints and the voluminous lit­ erature on this subJect has been difficult for the average physician. As an assimilation of the literature as well as a general review of the subject to date, this paper is presented. We define gas gangrene as an infectious form of gangrene, produced b7 the pathogenic gas-producing bacilli, occurring characteristlcalq in grossl7 contaminated wounds, and being char­ acterized b7 certain obJective and subjective findings. In this review I have attempted to deal onl7 with the common form occur­ ring in the extremit7. Following the various procedures I have attempted to arrive at the most modern and most widel7 accepted conception of this disease process at the present time. /''-....

EA.BLY HISTORY l

Hippocrates, writing of a ease of gangrene, although. it is not clear that it was of the emphysematous type, said, 8 Critin of Thasa commenced to experience pain in his foot, in his great toe.

He went to bed the same day. He ka.d a slight chill, some nausea, and then a little fever; he became delirious during the night.

On the second day there was swelling of the entire foot and of the ankle, which was a little red and t:ander; there ware present tiny black blebs, and he had a great fever. The sick one was entirely out of his head; he died the second day." (73). Celsus is thought by some to have known of the occurrence of gas gangrene in preg­ nancy for in his chapter on the extraction of the dead fetus we find, "It JD81' so happen tha.t the child m~ be distended with a humor, from which there flows a fluid with a fetid odor." (109). Following these early writings there is a long period during which the disease does not seem to have been recognized. Avicenna,

Guy de Chauliac, J de Vigo, and Ambrose Pare do not refer to it (73). But in Fabricus de Hilden•s works (Opera Omnia, Frankfort,

1776) we find mention of the condition. "It is my belief, 11 he says,

"That the principle cause of this· terrible ill is some venous humor which Nature has driven into these people.• (73).

Q:u.esn~, in 1745, in a chapter on "Gangrene of putrid disso­ lution of the humoral mass," gave Peyronnie the credit for being the first to describe and furnish exact observations of gas gangrene, and spoke of the "subcutaneous emphysema, the erysipelatous color 2 of the skin, and the rapidity of death" (73). We find that De la Motte, in 1771, published two observations which have been accepted by some as being cases of gas gangrene (73). In 1786, Thomas Kirk­ land knew it and called it gangrene of the "emphysematous type" (73).

Early in the Napoleonic Wars, during the nineteenth century, Larrey seemed to have known this disease. In some of his observa­ tions he spoke of the rapid progress of traumatic gangrene, which in a few hours spread from the limb and was often fatal in less than ten hours (73). Boyer, in 1814, mentioned its occurrence in fractures and also spoke of the rapidity of death, while Velpeau, in 1829, stressed it as a complication of fractured limbs and con­ sidered the emphysema of grave importance (35). In his experience, death was the outcome in most cases. Du.puytren, in his lectures under the name of "spontaneous emphysema," described a condition occurring in trauma resulting in rapid decomposition, and in 1836, we find Martin de Bazas publishing a case of "foudryant gangrene" which followed a crushed foot and in which death occurred in twelve hours (73).

Malgaigne recalls a case of rapid termination a£ter emphysema complicating a fractured limb. He looked for the real cause. "I think," he said, "That there occurs under the influence of shock and stupor a special change which attacks life just as excessive cold will kill the sperm in an egE' (73). For the first time the gas escaping from the emphysema was analyzed, and was found to be 3 inflammable as well as·showing the presence of lfTdrogen Sulfide. Renault and Chauveau were among the first to create gangrene in animals (73).

At the meeting of the AcadeJD7 of Sciences on Oct. 11, 1849, Cha.ssaignac asserted that certain gangrenes with emphysema should be considered as aaving •a poison far in excess of the mechanical inJur7. 1 He described tour cases the next year which showed what he called •empoissonnement traumatique1 (73). Maiasonneuve, to whom is often mistakenly given the credit for the first clinical description, reported to the AcadeJD7 at a later date (Sept. 12,

1853) two cases of gas gangrene and delcared that there existed a certain variety of traumatic gangrene to which he gave the name of •gangrene :foudroyante1 in which, first, putrefying gas developed in the interior of veins during life; and second, that this gas circulated in the blood and caused a fatal poisoning. Later, in developing the doctrine of 1 pneumohaematuria1 he considered thie as a variety of septicemia (69). Du.ring the Crimean War, Pirogoff with the Russian, and Salleron with the Allied Forces, both noted this condition and wrote about it (107). Pirogoff spoke of it as 1 primary nephritic gangrene,• while Salleron reviewed 65 cases collected from the casualties of that War. Dolbeau emphasized the idea that the "autoin.fection" was al'W8.1's fatal, and declared himself strongly in favor of immediate amputation (73). Billroth busied himself 4 for a time with it, and considered the cause to be a decompositian of the mortified elements occurring in the disease. Gurlt dis­ cussed it in his book on bone surgery (1862) (73). Bottini is given credit for being the first to demonstrate the infective nature and transmissibility of gas gangrene (112). In the .American Civil War, there is no record of gas gangrene as such. In fact Keen, who served as a military surgeon, stated that he never saw a case (53) •. It was, howiver, observed in the

J'ranco-Prussian War. 1'7att observed it at the seige of Paris (73), and J'rer;y mentioned it as occurring in Belfort. Passow declared that it was discussed at a meeting of the German militar7 surgeons in Orleans (73). In his excellent monograph on this subject, !rifaud has collected 123 cases occurring in civil life previousr to 1883 (73). In 1887, Jurgensen described a case, and attributed the gas to a gas forming microbe (112). 11th the appearance of the

1Bacter1ological Era," the organisms found associated with the cµ.sease were investigated b7 ID8D1' workers. Pasteur discovered the Vibrion Septique (78), Koch the bacillus of malignant edema (73), and Welch the gas bacillus (Bacillus Welchi) (114). He was unable to demonstrate spore formation in the aarl7 cultures, but this was noted by J'raenkel who also described the Welch bacillus the following year (32). !he clinical aspect of the disease was investigated and 5 described b7 Stolz in 1902 (112), Stewart in 1905 (98), Cramp ia 1912 (17), and Simonds.in 1915 (97).

During the World War great interest was aroused in this disease and the literature which appeared during the 7ears 1914- 1919 was enormous. Among a great number of fine papers, perhaps the most comprehenaiTe were the Surgeon General's Report (84) and the Report of the Medical Council of Great Britain (95). IHCIDDCJl .6 While a study of the available statistics leaves one with the impression that gas gangrene has been comparatively rare in civil life, it became of extreme importance during the World War. The multitude of grossl.7 contaminated wounds, occurring in the trenches amid extensively manured soil, served as an ideal type of injury in producing the infection.

In Trifaud1 s monograph on the subject, he has listed 123 cases occurring in civil life before 1883 (73). In 1900, Welch was able to collect 46 proven cases of gas bacillus infection. Sixteen cases were observed in Baltimore, sixteen others were recorded by other American observers, and only 14 were reported abroad (114). Cramp, in 1912, found-187 cases in the literature, and reported 25 cases ,/ from the wards of Belevue Hospital during an eight year period (!7). Weintrob and Messeloff, in 1927, reported 85 gas bacillus infec­ tions itreated in the Bel:""'~e Hospital from i911 - 1926. There were 618,105 admissions during this period, or one case for every 7,310 total admissions (110).

Boland reports that in the Gra.dy Hospital in Atlanta, Georgia, during the seven 7ear period ending in 1929, eighty compound fractures were encountered in Negroes, with 19~ developing pa gangrene. During the same period, of 97 cases of similar injuries occurring in white people, onl7 7~ developed gangrene. He brings up the question of whether or not the Negro is not more suscepti- ble to the infection (94). 7 Millar, in 1932, colJfcted 607 cases of gas gangrene occurring in civil life, exclusive of obstetrical infections. Only those subsequent to the Lister Era were taken. Males were affected six times more frequentq than females. The third decade of life furnished the greatest DWDber of cases. Cases were reported from all parts of the world, and no seasonal variation was app!.rent. This, as well as the above reviews, leaves the impression that gas gangrene is rarely seen in civil practice (73). It must be remembered that there are m8JJ1' more cases occurring throughout the world than are recorded in the literature. Also any one series is perhaps not a fair cross section because of the l:mman tendency to report the bizarre and unusual cases. Stone and Holsinger reviewed 67 cases occurring at the University of Virginia Hospital from 1921 - 1933. In this series gas gangrene represented an average of 1/1035 hospital admissions, which seems to be rather;:high. Of interest was the greatly increased incidence since 1926, which they attribute to an increasing number of traffic accidents, the more general use of machinery in the South, and increased industry; all of these would favor production of inJuries which are prone to develop gas bacillus infections (99). As regards military incidence, Gross has published a rather extensive anlaysls covering the years 1916-1917. He states that during the early p;irt of 1916 he p;issed 2,796 wounded men through his ambulance with 3.6~ developing gas gangrene, while during the 8 latter part of the same 7ea:r he passed 1,676 men with 1.9% developing the infection (43). Emery, however, emphasized the small percentage of gas bacillus contaminated wounds which developedc1.inical symptoms (27). Mairesse and Regnier state that they examined 1,016 wounded men bacteriologically, and found only 297 showing contamination with the gas bacillus (66). Sieru and Mercier reported fewer than 0.5% of their wounded developed clin­ ical gas gangrene (96). Pettit reported a rather complete summary gathered from the Transportable B'ospi tal fa during the Great War. Of 4,377 patients that were wounded in action during the latter part of 1918, 5.~ developed gas gangrene. This is a rather high incidence, but it should be noted that this hospital received only those seriously wounded. Gas gangrene was a most important cause of death, accounting for 17.0% of all deaths. Of 890 wounds examined bacter­ iologically, 53% were found to contain anaerobic bacilli; it is 81 interesting fact; however, that of this number, only 34~ at ~ time developed clinical evidence of gas infection. It is thus seen that in their experience, at least, over two thirds of the wounds contaminated with anaerobes did not develop gangrene (SO). The American Expeditionary Force in France had 1.08% of all wounds of the soft rarts develop gas gangrene, according to the Surgeon General's Office (84). The official British Expeditions,ry Force report gives an incidence of 1.0%. The number of cases 9 varied in the big pushes, and when it was not possible to treat the wounded quickly-, it was of course much higher (85). •

ETIOLOGY 10 We have seen that Fabricus de Hilden mentioned gas, gangrene in 1776, and stated that in his opinion the principle cause was a venous humor which "Nature had driven into these people" (41). Malgaigne, in 1839, in attemptin& to determine the real cause, stated that there occurred under the influence of shock and stupor a special change which attacks life Just as excessive cold would kill the sperm in an egg (73). During the next few years, numerous accounts appeared in the literature conce~ng cases in which gas wasfound in the vessels at autopsy, and various explanations were advanced to cover these.

In Maissonneuve 1 s classical description o~ the clinical syndrome in 1853, he believed that putrif7ing gas developed in the veins during life and circulated in the blood, causing a fatal poisoning. Later, in developing the doctrine of •pneumohematuria" he considsred this as a variety of septicemia (73). Bill1'oth considered the cause to be a decomposition of the mortified elements occurring in the disease. (73). Ma1', in 1857, reported three cases in which air was found in the vessels post mortem. One of these seems to represent a very clear case of typical gas gangrene, occurring in a man who in;Jure.d. his toe. At autopsy, several hours later, air wasfound in the . vessels, heart, liver, and subcutaneously in the leg. He attempted to dete:miine the probable source of the gas, and raised the IPJ.estion of whether or not air can enter the circulation during life as well 11 as whether air could ~e generated in the boq. He concluded that air could enter the veins from a local pathological condition and cause death. Little did he realize just how close to the truth of the matter he actually was (70). One -,.ear later he again reported two similar cases, and again seemed to be concerned over the possibility of air being generated in the body during life.

(69).

Greene, in 1887, reviewed eighteen such cases in the liter­ ature, and concluded that air could and did enter the circulation during surgical operations, deliveries, etc., and caused death

(41). The discussion turned generally around the question whether the gas was atmospheric air or the result of putrefaction. 'fhis question in most cases could only be solved by bacteriological examination, and efforts began to be directed along this line. In 1891, L8'V7 isolated a bacillus from a gaseous phlegmon of the pelvis and thigh of a puerperal woman. 'fhis organism was anaerobic, gas-producing, non-motile, short, small, delicate, stained b7 Gram, grew in long threads and chains of thirty or more, and formed Anthrax-like colonies. lto experiments upon animals wwre made (112). In a subsequent article in 1895, Levy declared that this bacillus was identical with J'raenkel • s bacillus phlegmonous emphysematosae (112). Welch and lfu.ttall, in 1892, reported their classical discovery of the bacillus which the7 termed Bacillus Aerogenes Capsulatus, 12 but which is no• known as Bacillus lfelchi. This occurred in a man with a substernal aeneurysm with recurring rupture. At autopsy the entire boq was found to be markedly emphysematous. '?he blood was found to be rich in bacilli, and extensive bacter­ iological studies were made. The organism was also injected into laborato17 animals and the same post moretm findings were obtained, with recove1"7' of the organiem. These men therefore concluded ths the organism was the cause of the condition, and called attention to the large number of reported cases of similar autopsy findings in the literature in which no cause could be found. The bacillus was isolated in pure culture and its morphological and biological aspects were extensivel7 studied. The7 stated that there could be no doubt that the gas found in the vessels and organs at autopsy was not atmospheric air, but was produced b7 the bacillus. Further, the7 concluded that the organisms had entered the bodJ' through the anaer;ysmal sac through the external openings on the anterior chest wall. The7 also stated that in their opinion, the entrance ~f the gas and bacilli into the circulation was concerned lrltth the death of the patient, however the7 expressed themselTes with reserve on this point. (114). The first observations of the bacillus aerogenes capsulatus following the report of Welch and Nuttall were made by E. Fraenkil, who published, in JanU8l'7, 1893; a preliminar;y report, and later in the same 7ear a monograph concern.int gaseous phlegmons. Fraenkel 13 inai:es_..DO mention of the previous discover7 of the same organism )7 these two men, and evidentl7 was unacquainted with their work. To Fraenkel belongs the credit for the demonstration of the causal relationship of this bacillus to the affection callad., at that time, gaseous phlegmon, emphTsematous cellulitis or gangrene, gangrene gazeuae, etc. He reported the results of hia investiga­ tions of four cases of gaseous phlegmon. Two of the cases followed subcutaneous injection of drugs, however in mne of these cases was gas found at Blltops7 in the vessels or organs. The bacillus isolated

b7 Fraenkel correpponded in every wq as regards morpholodcal and cultural characteristics with the bacillus aerogenes capsulatus, and to it Fraen1tel gave the name bacillus phlegmons emphysematosae.

(32). The probable identi t7 of Fraenkel • s bacillus of gaseous phleg­

mon with the bacillus Of Welchi was recognized by Mann, in an article published in 1894. He isolated the bacillus from a case of gas gangrene resulting from a finger injUJ7, and stated that the organ­ ism was capable of growing in the living body with the production ot gas gangrene without the ent17 of the gas into the blood vessels. This is the first reported case which recovered after the nature of the infection had been established. (67). The next publications concerning the bacillus aerogenes cap­ sulataa were those of Graham, Stewart, and Baldwin in 1893. The;r reported a case occurring following an abortion, in which at a11.topq l""' 14 enormous, generalized emphysema was found. This case was recog­ nized before the autopsy as probably referable to the bacillus described by Welch and Nuttall. The significance of this case is that it afforded positive evidence that the gas bacillus might invade the blood and produce gas widely distributed over the body during life. Bacteriological studies identified the organism as the bacillus aerogenes capsulatus (39). In 1896, Flexner and Welchi published an extensive paper covering 23 human cases ~th various pathological manifestations of •heir bacillus (113), and 1900 Welch published another study ~ the same nature (112). In this report he states "While it has been demonstrated that various bacteria may be concerned in producing gaseous gangrene, it is now evident that the bacillus that I dis­ covered in 1891 is the one whose causative agency is best established."

The bacillus of malignant edema was first discovered by Pasteur in 1876 after infecting animals with putrid flesh. He termed thts the Vibrion Septique, and classified it among his 'septicemie1 (?.a). Several years later Koch found the same bacillus in the human body, and gave the name bf bacillus of malignant edema to it (112).

Gwyn, in 1899, reported a case report, which, although it at no time presented symptoms of gas gangrene, nevertheless gave posi­ tive blood cultures for the presence of a bacillus which he states he identified as the bacillus of Welch. He con:iuded that the organ­ ism was one of attenuated virulence, and that it was apparently held 15 in check by the bod1' during life. 'fhis was the first case in which the organism was cultivated from the circulation during life {44). Bare, in the same 7ear, reviewed 22 cases with ni:aa deaths {45). Kausch, in 1915, stated that in his opidon the condition was due to Fraenkel1 s bacillus alone {52), however Selter, in the same year, examined 14 cases by means of direct smear and culture, and concluded that gas gangrene was not alwqs caused by this bacillus, but might be produced by other anaerobic organisms {95). Jordan, one year later, stated that "While other organisms have been identified w!iih gas gangrene, they are all very similar to the Welch bacillus and ~ be referred to collectively as •gas bacillus• {107). Weinberg published a rather extensive rettew of the bacter­ iology in 1916, and stated that B. Welchi was very commonly found in. the condition, while the Yiblion Septique was found in 4% of the cases only. He produced the infection experimentally in Guinea Pigs and showed that trauma to the muscles and vascular embarrass­ ment were of great importance in its production {108). It was about this time that the literature appeua to be literally flooded with articles dealing with this condition. The infection of wounds by gas producing organisms was by no means new; as I have shown, attention had been repeatedly called to infections in previous wars which had resulted in an emphysematous condition of the bod1'. In 16

the World War, however, the nature of the battle ground, the con­

centration of large numbers of individuals, and the underground

methods of warfare all combined to accentuate the presence of this

infection and caused it to assume a prominent role in military

surgeey.

The Welch bacillus had been long known as a gas producing

organism, capable of infecting wounds. Until the outbreak of the

World War, surgeons and bacteriologists had not had sufficient

experience to justify a positive opinion, as regards the etiolog­

ical relationship of this and other gas producing organisms, in

the production of what had been called gas gangrene. The reason

for this reservation had been due largely to the fact that numerGUs . ,,,.,.... other organisms had been recorded as accompanying an infection of

this kind. In addition to this, chains of cocci organisms had

been thought at times to have been able to assume a gas-producing

role. Among other bacilli found to be present in gangrenous tis­

sues were the colon, proteus, and other putrefactive bacilli. For

several months after the World War began the unidentified gas pro­

ducing bacilli, resembling the Welch bacillus, were known as bacil­

lus perfringen.s, largely on account of certain cultural character~

istics of the Welch bacillus. However as time went on and the

bacteriological technic of war hospital laboratories became more perfected, it became apparent to careful observers that the perfring­ ens was really a strain of the Welch organism. 17 Bull and Pritchett were the first to demonstrate a true exotoxin in B. Welchi cultures. This work was pb.blished in 1917, and the7 showed that the toxin was specific, thermolabile, and antogenic. The7 also stated tha. t the toxin was a. complex of a hemol7sin and another poisonous bod.J' producing inflammation and necrosis of subcutaneous tissue and mu.sole (13). In a later pub­ lication these same men attempted to determine whether or not one toxin was common to all strains of B. Welchi. The7 concluded that in the 22 different strains that the7 had investigated, all had a similar toxin (14). In 1919, Fa.siani referred to an article b7 Conradi and Bieling in 1916, in which the7 stated that the different anaerobic bacilli did not constitute different and distinct strains, but rather that they were transformation stages of one species only. Fasiani expressed the opinion that this conclusion was erroneous, and that the varioua bacilli did constitute different species (28).

Henry, in 1923, ellph~si•ed that the toxin of Bacillus Welchi was actuall7 a myotoxin (47). Gemmell, called a1119ntion to the pos­ sibilit7 of coJllJIU.llicating the clsease b7 fomites, and pointed out that the spores resisted ordinary hospital sterilization (37). A year later he stated that in his experience, those cases in which the Vibrion Septique predominated greatly offered a mu.ch graver prognosis (37). Gage, in 1932, called attention to the almost constant 18 presence o:f' the Welch bacillus in wool cloth and on shot gun wads. He demonstrated that he was able to produce the infection by in­ serting some o:f' this material into traumatized muscle (36). Krymov pointed out that the bacillus possessed the ability of lying laten' in the tissues 1br as long as 15 years before initiating clinical signs of the infection, and reviewed several cases of alleged nature (58). J'inedl.ver stated that, although the Welch bacillus was commonly present, the possibility of a symbiosis is certain, other organisms being Pasteru1 s Vibrion Septique, B. edemateins, B. histo~ticus, and B sordelli. (31). Touraine, in 1936, emphasized the possibility of the infec­ tion 1 s :f'ollowing hypodermic injection. At that ti.me he had col­ lected 83 such oases (102). At the present time the recognized group of organisms con­ sists o:f' about 25 anaerobes and 15 aerobes. These bacteria have a wide distribution in nature. The organisms usually concerned in gas bacillus infections are as follows: (1) Bacillus Welchi (B. perfringens, B. aerogenes capsulatus) is the greatest producer of gas and is most often isolated in gas gangrene. It may be found alone, but is usually associated with other organisms. Aerobic sapro:f'ytes seem to incite greater path- • ogenicity. It attacks muscle with avidity, as a result, as many have suggested, of the glycogen. Vincent found this organism in 19

82% of gas gangrene infections during the war (105).

(2) Vibrion Septique is a rather rare, slender, motile, sporing organism which also produces a classic form of gangrene. It produces less gas but moBe edema, and therefore predominates in edematous lesions. Most bacteriologists feel that its patho­ genicity is anything but feeble. The clinical manifestations of this bacillus begin several days later than B. Welchi and seem to be more superficial. Thiscorganism is found in l~ of gas gangrene infections according to Vincent (105).

(3) B. Edematiens is pleomorphic and ~ resemble Vibrion

Septique, B. Sporogenes, and B. Tetani. Its toxin produces a special white edema which more or less masks the gas infiltration.

Vincent and Stodel state that this organism is found in from 4-5% of cases of gas gangrene (105).

(4) Bacillus Sporogenes is a common anaerobic associate with the same morphological characteristics as Vibrion Septique, but it is considered to be non-pathogenic. It is motile and is responsible for the putrid character of the wound.

Since these organisms a.re so widely distributed, the question naturally arises as to why one does not see more of these infections.

The answer is probably found in the experiments of Teissier, who demonstrated that gas forming organisms in themselves have but l~ttle power to attack the tissues, but, when asQociated with other organisms, they rapidly produce the typical picture (18). Inoculation with 20 either B perfringens or B edematiens produces a hard edema which slowly disappears. When growths of aerobic bacteria are added to these cultures, a severe infection results, and the an'-mal rapidly dies. Vincent has shown that, if one injects separately into two ·Guinea Pigs attenuated B. Welchi and Vibrion Septique, neither alone will produce the gangrene. But if one injects the mixture of either of these with B. sporogenes, a typical gas gangrene will result (105). PATHOLOGY 21 Emrys-Roberts and Cowell have presented a very comprehensive summary of the local pathological changes (27). They have divided their discussion into the macroscopic and the microscopic changes occurring; (1) at the.wound surface, (2) in the area of dead muscle, (3) at the spreading edge, and (4) in the contractile part beyond. As regards the macroscopic changes at the wound surface, they state that in the early cases the damaged and infected muscle f_ibers mq be seen to be pale in color and non-contractile, while the wound surface is covered wih a thin film of a viscid greenish­ yellow fluid. On close examination fine pink lines, indicating the •pread of infection into the muscle, run along the course of the perifaseicular connective tissue. In the more superficial wounds, the surface is at first a duslcy' red, later becoming paler, then green, and finally black. This is due to the local contusion producing interstiUal he~orrhages, the blood from which is imtned­ iately attacked by the products of the bacteriological growth. There is no actual pus exuded from the wound surface, although a thin, clear, foul smelling fluid does escape. Underneath the infective process continues to develop, softening occurs. The surface becomes crepitant to the finger, and soon reaches the final stage of black deliquescence. Microscopically the •uperficial, obviously necrotic, muscle will be found to be composed of distorted, swollen, fragmented fibers, in whose meshes are large numbers of polymorphoaerobic organisms and cell debris. The vessels are 22 quicl:ly damaged and thrombosis takes place. The entire mass is effectively bound in a fibrinous reticulum, which, by binding the pieces of dead muscle and the leucocytes, prevents the forma­ tion of typical pus, and accounts for its absence in gas gangrene.

In the area of ~muscle in the very earliest cases, if the muscle is examined immediately below the wound surface macro­ scopically, it is found to be firmer than normal and no longer contractile. There is no change in its color, but there is a distinct lack of luster and translucency. Soon, however, the sequence of color changes appears. The normal red is lightened and beoomes pink, thereafter running through the greys and greens to the final black. Gas production begins at a variable time after the death of the muscle, usually it does not occur until many hours have elapsed, so that it mu.st be regarded as a late manifestation. At first minute bubbles a.re found, these coalesce and rapidly im:trease in size, giving the dead muscle a spongy appearance. As gas is produced in greater quantities, it forces its Wf3:¥ along the planes of least resistance; in this way the fascial sheaths become distended with gas and a mechanical ischaemia is produced from the blood supply being obstructed. This acceler­ ates the spread of gangrene. Massive thrombosis, apart from those resulting from the trauma, are not a concomitant of the typical process of gas gangrene. Microscopically the muscle fibers them­ selves have lost all normal characteristics of stria.tion and 23 staining properties. They are swollen, distorted, and fragmented, present longitudinal splitting, and are separated from the surround­ ing interstitial tissue by distinct spaces. Myolysis frequently proceeds to such a degree as to lead to entire disappearance of the portions of fibers involved. Many of these fibers are in process of a.ctive phagocytosis. The leucocytes decrease rapidly in number as we,proceed in the direction of the spreading edge, as do also the bacteria. All stages from vessels with normal walls on the one hand, and vessels whose walls have been completely lysed on the other, can be seen.

In advancing cases, a.s we proceed to the spreading ..e.W of the infection, a point is at last reached where non-contractility ceases, and the muscle again reacts to stimuli. This line of junction is found to extend across the muscle in an extremely irregular fashion, at times being demonstrated at some distance

- often several mm - in front of the dead muscle fibers just described. This is possibly the most interesting area of all. Here the proportion of dead to living fibers is reversed, and we find an occasional dead or dying fiber among many living ones. At' the spreading edge there is no indication at all of the vascu­ lar change in those cases in which the effect of the original trauma can be ruled out. The demonstration, histologically, of the bacilli is very difficult here, but they are known to exist there because their presence can be demonstrated by means of 24 cultures taken from this area. The soluble toxins of the bacilli exist in the perifibrillar space and are here absorbed b7 the muscle fibers. Traveling in the direction of the long axis, they kill the fiber as the7 advance. Hea'V1' bacterial infection, com­ bined with inefficient drainage at the surface, leads to increased absorption of the toxins, and so hastens the advancing death of the individual fibers. Similarl7, the more damaged the tissues and the greater the degree of blood extravasation and thrombosis, the less the resistance there is to the lethal process. Hence the astonishing rapidity of the advance in certain cases, more espec­ ially if, in addition to the local loss of resistance, we have a

lower general resistance resulting from fatigue, shock~ and hemor­ rhage. Lastly, we can examine the contractile part in advance of the spreading edge. In the absence of traumatic bruising effects, vas­ cular lesions have never been encountered. It must be remembered that traumatic interstitial hemorrhage is quite commonly met with at a considerabl- distance from the wound. No other sign .of macro­ scopic pathology can be found here. Microscopically, we find a continued development of the •ibrinous leucocytic l81'er, in such a manner as to form a distinct line of demarcation between this 181'er and the underlying normal muscle. There is usually a sudden

transition from the infiltrated l~er to the healthy muscle; while within the 191'er of fibrinous exudate the muscle fibers, where 25 recovery is taking place, are found to be dead and in the process of phagocytosis. The perifibrillar and perifascicular spaces contain the anaerobic toxins which by reason of their antichemio­ tactic properties repel leucocytes. We are, therefore, justified in s~ing that the greater the mass of leucocytic aggregation, the better the defense is proceeding. Later, when the·stage of recov- ery is still further advanced, the fibtinous exudate with dead muscle, is shed in the form of sloughs; revealing, beneath, the establishment of true granulation tissue, with loops of capillaries being formed and remains of muscle fibers undergoing absorption.

This is a sign that the underlying tissues have regained their vital properties. Leucocytes, no longer bound in the messes of the fibrinous reticulum, are freely permitted to return to the tissues and to be shed as pus. Regeneration of such a highly spec­ ialized tissue as muscle fiber must necessarily be of a very imperfect nature, and many investigators question the possibility of any real replacement of lost muscle tissue (75, 20).

Kausch, in 1915, described three forms; the mild, in which the infection is largely limited to the subcutaneous tissue, the severe, in which muscle involvement predomi&ates, and the fulminating, in which all local tissues are concerned alike (52). Albrecht, 1916, reported that in his opinion death was due largely to a direct action of the toxin upon the heart. He also maintained that in many acute cases that there wa.a an acute failure of the Adrenal, 26 and stated that in such cases he had found a decrease in lipoid substance in the Adrenal (l:}. Ad.renal depression, as evidenced by a dim:t.nution of lipoid substance in histological section, was again referred to by later workers (15,104,5,64). Wallace, in 1917, studied the color changes occurring in the muscle and skin. He reported that the area first became a pale color due to the swelling, whi

T~lor believes that the chief agent at work is the evolved gas which by its mechanical pressure inhibits the blood supply, devitalizes the tissues, fragments the muscle, and scatters the 27 infection (101). If it is true, however, that gas production, except in the fulminating type, is a late stage of gas gangrene, '·-- then it can not be regarded as the chief factor. This view, as

I have stated above is taken by Emrys-Roberts and Cowell (27). Bazzaboni gives complete autopsy reports on a series of cases.

Be states that the heart is pa.le, flacid, and dilated, especiall7 the auricles. Microscopically the heart shows a separation of the muscle fibers. The lungs commonl7 present hypostatic congestion

with foci of bronchial pneumonia, while hi~tologicall7 hyperemia and interstitial hemorrhage are seen. The tb7roid gland is nega-

tive. The kidneys, stomach and bowel·are hyperemic. The liver n enlarged and hyperemic, while on section it presents a diffuse fatty degeneration with multiple foci of inflammatory infiltratian. The changes in the spleen are characterized by vasodilatation and hyperplasia of the ma.lpighian corpuscles. The adrenals are intensely

~peremic and often hemorrhagic. The retroperitoneal nodes are hyperplastic (82). Bingold states that in his opinion the bacteremia is one of the chief contributing causes of death (5). CLINICAL PICTUBJI 28 The symptoms and signs arising from limited foci of infection with anaerobic bacilli are in keeping with the pathological changes outlined above. The disease occurs a variable time after the

reception of a wound, particularl7 if this is lacerated and assoc- iated with much trauma and hemorrhage into the tissues. or with the fracture of a bone. Losa of blood leading to shock, as well as any previous disease tending to impair the blood supply to the part (diabetes, arterial disease) act as predisposing factors and greatly , aggravate the picture. lllmrys-Roberts and Cowell consider three main clinical types in their discussion of the symptomatology of gas gangrene infections

(1) The common type which occurs in neglected wounds 12-24 hours · after the injury, (2) The fulminating type, where the p:1.tient, especially if untreated, mq be dead in a few hours,

(3) The del81'ed type, *1th a slow ~nset so that the condition only becomes established several d81's, weeks, or even months after the injuey. (A) THE COMMON TYPE: One of the earliest qmptoma is pain coming on about 36-48 hours after the original injury, and becoming rapidly more severe. A marked rapid rise of pulse rate about the same time is to be expected. Such a combination of symptoms should J..ead one to examine carefully- the injured part. The area does not 29 have the physical. characteristics of a pyogenic abscess; there is no redneSB or increased skin tempera.ture. The skin overl7ing the lesion is exceedingl.7 tender with alternating anemic and dis­ colored redish black patches. The discharge from the wound is not purulent, but an irritating brownish watery fluid with a sickly foul odor. Later as the edema increases and the gas devel­ ops, it becomes dusq and bronzed in appearance. Wallace has carefull7 studied these changes in the color of the overl7ing skin, and feels that the7 are of great importance in the following the progress of the pathology (106). The systemic signs accompa!J1'ing such an infection afford a strong contrast with those of other t;ypes of localized infection. I have mentioned the ver7 ~id and easily compressible pulse; there is an alarming fall of blood -pressure, and all the signs of complete collapse are noted. Res­ piration becomes rapid and shallow, and the patient runs a mod­ erate fever, usual}T from 100 - 103 F. Vomiting is a distressing feature at times, and in the last stages JDS1' become black from petechial hemorrhages. Mentall7 these patients are often perfectly clear, and it is not uncommon to see a man smoking a cigarette or reading a newspaper a few hours before death. Mild delirium is noted at times but is not common. Later, as true gangrene sets in, the tissues become a dirty green and black color. The presence of gas cannot be detected in the early stages, and must always be con­ sidered as a late phenomena. The best means of detecting its 30 early presence is by stroking with a flat instrument, which gives a distinctly crepitant note. The bubling of gas from the wound also is a late process. X-rST reveals a few, dark fine streaks along the course of the muscle, a few hours la.ter, however, the gas collects in small pockets and gives a typical mottled appear­ ance to the film. The blood shows no great increase in the leuco­ cytes, but indicates a severe anemia. Blood cultures are onl7 rarely positive (5). If such cases are untreated, the infection runs its cours, and ends fatally in 12024 hours after the date of injury. (B) THE FULMINATING TYPE: In the common type the rapidity of the spread was striking; in this type the speed of the sequence If events is even more dramatic. This is especially apt to follow conditions where shock and blood loss are marked, and it is this symptom complex of shock, hemorrhage, and exhaustion, associated with the anaerobic infection, that combines to produce these cases.

Such patients when first seen are usually cold, pale, restless, and usually vomiting. The pulse is often imperceptible at the writ and the systolic blood pressure is around 50 mm of mercury.

Locally thw wound presents a very similar appearance to that described above, but extensive gas formation may occur within a short time. When in this state the patient cannot stand much surgical interference, and death oftentimes takes place in 10-24 hours, or less, after the initial injury. 31

(C) THE DELAYED TYPE: Here both the local and ge~al resist­ ing powers of the indiv14ua.l have succeeded up to a point and the.it latent infection is limited to the surface of the wound. At a variable time inte?Tal, and oftentimes following some new stimulus such as injury or operation, constitutional symptoms appear, and the disease runs a tri)ical co\U"se. Krymov has emphasized thie property of latency, alXieven claims that he has found cases in which such latency existed for as much as 15 years after the initial infection and before signs or symptoms developed (58). DIAGNOSIS

.If"". The diagnosis of gas bacillus infections must depend not only upon one•s ability to Judge clinical findings, but on the laboratorr findings as well. The points in the clinical picture which are of most importance in making *he di8€1losis are: (1) pain, which is the most common symptom (2) rapid pulse, which is the ma.t common sign (3) swelling (4) local discoloration (5) crepitus (6) the characteristic odor As regards laboratory aids, those of undoubted diagnostic import- ance are: (l) bacteriological findings (2) the roentgenogram (3) various animal injection tests Nearly all who have written on this subject agree that pain of severe degree is probably the earliest 111ptom found in such cases. Acoompanying this pain is the swelling, which is 11.sually of a firm type, without much fluctuation, until necrosis is well established. Probabl7 one of the most significant of the early signs is the elevation in thepulse rate. While this is, of cour11e, not diagnostic of gas infections alone, yet it is one of the ear- liest and most definite signs. As a rule it is way out of propor- tion to the elevation of temperature. The color changes have been described in detail. Crepitus is one of the signs looked for most frequently and considered so characteristic. It must be remembered, however, that this is a comparatively late finding. The odor is 33

said to be characteristic , however it is interesting to note the

various attempts to describe it in the different accounts. It is

putrefactive, offensive, and "mousey," however he who attempts to

diagnose the condition on the odor alone will come to grief.

Bacteriological findings are oftentimes of value to the

clinician. A smear and culture of the wound should be taken in

all doubtful cases. If the smear shows organisms of suspicious nature to one familiar with the examination of such smears, Ghormley

advocates that the institution of treatment is justified (38). !ile

report of the culture will necessarily be delayed and one should

not wait to receive it before beginning treatment when gas gangrene

is suspected. It is, however, of value in fonfirming latent infec­

·""""· tions. Reeves has advocated a capsule stain as the most reliable single laboratory procedure, claiming that B. Welchi is the only

pathological anaerobe with a capsule (83).

Schwartz, in 1915, called attention to the appearance of the gas in the tissues upon the roentgenogram, and advocated this

procedure as an aid in making an early diagnosis (56). Since that

time, many investigators have empaasized this extremely valuable

dia.gnostif aid (63, 91, --19, 75).

Various animal injection procedures have been proposed, but

none have come into wide favor as yet. Jennings, in 1923, advocated injection of suspected matter into the ear vein of the rabbit. The

animal was then killed by a blow on the head, and incubated for 12 34

hours. With the presence of B Welchi.the carcass was found to be

greatly emphysematous and the organism could be recovered from the

organs, especially the liver. This test is rarely necessary, how­

ever (50). Nerb, in 1927, advanced a plan for injecting suspected

material into the liver af the Guinea Pig, taking care to trauma­

tize the liver in the injection. This animal was then killed, incubated for 12 hours, and examined for similar findings (76).

Reeves has thrown some doubt upon the accuracy of these two tests,

by demonstrating th.at in each case similar results can be obtained

by use of sterile saline injections. (83).

,,...... \ 35

The treatment of gas gangrene of the extremities resolves itself into an early recognition of the condition and the immediate institution of all prophylactic and active therapeutic measures available. The ever mounting number of cases of this condition seen in civil life mq be attributed, at lea.st in part, to the hesitancy •o utilize proper measures, procrastination, or to sheer ignorance of the morbid prognosis of all crushing injuries of the extremities. As early as 1893, Fraenkel advised incising the parts freely so that air could reach the diseased tissues, and also stated that the application of an oxidizing agent such as KMn04 or H202 might be of value. This statem•nt was made only two 7ears after Welch announced. the discovery of his organism (32). Mann, in 1894, reported a case treated with long, free incisions and hot HgC12 packs (67). Prior to the World War the treatment of this condi­ tion tended to be radical, and it became generally held that early amputation was always indicated. In 1912, Cramp advocated more conservative measures, and reported several cases treated according to Fraenkel's original recommendations, with encoura&ing results (17). Local excision of diseased tissue was practiced occasionally in civil surgery, but it was not until the World 'far that the value of debridement, as we know it to~, was full.7 appreciated. During the Great War the use of specific serum, both prophylactically and therapeuticly, was introduced. 36 (A) PROPHYLAXIS

The pr~phylactic treatment of gas bacillus infections becomes largely an evaluation as to what wounds are apt to give rise to the infection. In all injuries in which there has been much maceration or crushing of tissue, one should be on his guard for the possibility of anaerobic infectio~. If any suspicion of gas gangrene arises, there should be prompt debridgement of the wound. Although some men have gone so far as to recommend immed­ iate amputation as a means of prophylaxis, the consensus of opin­ ion seems to be against this radical procedure (56). Following the serologic work of Leclainche and Vallee (62), Sacqupee (87), Weinberg (108), Bull and Pritchett (13), and others, the use of this serum as a means of prophylaxis was intensively investigated. In 1917, Duval and Vaucher reported 50 cases in which a combination antiperfringens, antioedematiens, and antivi­ briona.ry serum prepared by Weinberg and Sequin was injected pro­ phylactically. In none of the patients did gas gangrene develop, although all were of the most severely wounded type (24). In 1918, the same authors reported 281 cases in which severely wounded men were injected with serum from the Pasteur Institute, a pooled serum similar to the one of Weinberg. Here,

6.4~ developed gas gangrene with ten deaths or a mortality rate of 3.5%, which was lower than that which those authors call the usual mortality rate from gas gangrene in the severely wounded (16~). 37 They expressed themselves as being enthusiastic over this measure

(25).

Mairesse and Regnier, in the same year, reported that of

1,016 wounded men examined bacteriologically, 297 showed gas bacil­ lus contamination. These were given prophylactic injections as indicated by the bacteriologic report, and in 10% of the cases, gas gangrene developed (66). Many other investigators reported cases so treated during the latter ~ea.rs of the war, and in most cases expressed themselves as being greatly satisfied with the results (62, 26, 4, 49, 103, 86, 64, 2). In the Spring of 1918, the British made a considerable test of aero-therapy, using a weak, polyvalent serum containing anti­ toxin against the three gas bacilli and B. teta.ni. Prophylactic doeea were given to 15,000 soldiers; 15,000 controls were selected, and records were kept of those developing gangrene in both groups.

When all of the results were in, a careful review showed that there wasPno significant difference in the incidence rate. ApParently, however, the investigators were impressed, for they laid the fail­ ure to secure positive results to the weakness of the serum that was then available (103).

Early in the spring of the same year, bacteriologists who had been working in Franc~ on the Gas Bacillus problem were sent back to the United States to start the manu:facture, on a large scale, of an antigangre~us serum. For se7eral reasons the manufacture 38 progressed slowly, but, in the fall of 1918, about 5,000 doaea of serum reached the central laboratories of the A.E.F., and precau­ tions were made to test it on the wounded. In all about 2,500 were treated and 2,500 controls were selected. On the whole the results were encouraging, and it is believed that if the Armistice had not interrupted .the progress of the teat, a very favorable re­ port might have been finally rendered, which would have dictated the employment, as a routine measure, of the anti-gas serum in the future. (103). In November, 1917, the Third Interallied Contreas for the Study of War Wounds reported that the serum seemed to have given favorable results as a preventative, and one year later, the same conservative body reported that preventive serotherapy in the

French Aniry had reduced the frequency of gas gal'lgrene. (90). Penfold and Tolhurst, in 1937, reported the results of their wor~ on Guinea Pigs, in which they used alum precipitated suspens­ ions of formol toxins of l3 Welchi as an immunizing acu"· They demonstrated both active and passive immuni tey, and seem to be very enthusiastic over the future (79.). Thus we see that the use of serum as a prophylactic agent has beenwti.de)y urged. Although it is not as effective in the prevention of gas gangrene as tetanus antitoxin is in the preven­ tion of tetanus, it is felt by all investigators that there is sufficient evidence of its value to justify its use in the proph7- 39 lactic treatment of badly contaminated wounds. Five thousand units is usually considered as a prophylactic dose, but no hard and fast rules can be laid down covering its use, as each case must be considered by itself. It has been stated that the average morbidity of gas gangrene among those in the World War who had received prophylactic injections was around 0.6%, while among those who had not received the injections, the morbidity was around 2-3%.

The prophylactic dose of polyvalent gas gangrene anti-toxin is now prepared in conjunction with tetanus antitoxin for com- mercial sale. But for its cost it should be given in all street accident cases. For the private patient the cost can not be of any importance if the likehood of complication by this dread dis- ease m~ be reduced. In addition to sera, it is of importance to direct attention to certain other means of preventing the develop- ment of this condition. Shock must be energetically comaated.

Whenever possible either local, spinal, or nitrous oxide anesthes- ia should be used as the anesthetic, as ether and chloroform tend to the production of acidosis and so favor the production of gas infection. Blood transfusion has proven to be a valuable aid in comhating the anemia. Finally, in cases where anoxemia of the tissues ~ be predicated on the basis of a preexisting arterial disease, the use of a tourniquet, even though it may facilitate

' the performance of an operation, should be contraindicated a~tending 40 to further impair the nutrition of the tissues.

(:S) ACTIVE TREATMENT:

(i) SURGERY: The surgical treatment of wounds in which gas infection is present was explicitly outlined by the Medical Corp of the United States Army just before the battle of Chateau­ Thierry. This outline in the main applies to civil cases •• well as to military ones. a - Operate as early as the diagnosis is made. This has been emphasized by Kummell (59), Schmid (93), Kausch (52), Seefisch (94), and Schoessmann (92). b - In cases in the extremities, avoid the use of a tourniquet. c - Make incisions longitudinally, and half again as long as thought necessary in both skin and fascia. d - Go between muscles rather than through. or across them. Most surgeons have come to this conclusion (46, 114, 33).

i - Exci.se all discolored, noncontractile muscle, and all other infected tissue as well as a:n:y foretl!;n bodies. By the removal of an entire infected muscle or group of muscles, the spread of

infection ~ be stopped, and amputation ~ be avoided. Frankau (33) advocated this very important procedure, as did La.rdennois (60), Weinberg (109), and Schmid (93). f - Leave the wound wide open. Dress the wound with gause, laid in, not packed in. g - Carrol tubes should be placed deep in the wound for irrigation 41 only if it is sure that they will be properly taken care of. h - Parts that have inadequate blood supply, or those in which gangrene is already present, should be amputated at once.

j - When amputation is necessa17, disarticulation should be done when feasible. If this is not possible, the guillotine amp­ utation is the operation of choice. (2) SEROTHERAPY: During the later 7ears of the war in France, individual sera

were pre:pared against ¥arious organisms which had been found in gas infections. In 1917, Bull and Pritchett demOD!Btrated for the first time the presence of a true exotoxin 1n B Welchi cultures. Using this toxin, they then teveloped an antitoxin in rabbits, which the7 found to be curative as well as preventive in pigeons. By giving this serum prophylactically to the laboratory animals, and then comparing the sensitivity, With controls, to -he intr­ venous injection of the toxin, they were able to demonstrate a

passive immunity conferred as a result of the antitoxin. They concluded that the antitoxin was of definite value in animals, and that it should be attempted in man (113, 14). Further inves­ tigation, however, revealed that this, as well as other individ­ ual sera, was a failure, and the reason was not ve17 difficult to determine. As pointed out by Weinberg and Sequin (111), Selter

(95), and Nevin (77), the antisera prepared for one organism was

powerless to combat the growth of the other organisms which were

'"""

... 42 invariabl7 found in gas infections. Following this, polyval.ent sera were proposed b7 Weinberg and Sequin (111), Leclainche and Val.lee (62), and Vincent and Stodel

(105). Al though the polyval.ent serum did not seem to be specific in the cure of' the di eease, a prompt dropping in the mortali t7 was noted. Weinberg and Sequin reported nineteen cures in thirty caees

(111). BaZ)", reporting on the results of two years investigation into serotherapy, stated that encouraging results were being obtained, but did not give his mortality rate (4). Favorable results were also reported b7 Sacquepee (90, 88), Weinberg (108, 109, 110), a.lid Leclainche and Vallee (62). Rouvillois, et al, reported in 1918 the resul:ts of one year's investigation with polyval.ent serum. They compared cases treated with serum plus surgery with others treated with surgery a.lone, and stated that the addition of the serum reduced their mortality by 50% (86). Sacquepee and Vezeau de Lavergne presented experimental evidence favoring the use of serum. They were able to reproduce the infection by the introduc- tion of macerated infected muscle tissue into the leg of Guinea Pigs. They then demonstrated that the addition of serum either prevented development of the disease or greatly alleviated it (89).

Van :B·euren, in 1919, stated that while improvement in war results were being obtained by surgery alone even before the introduction of s•rotherapy, the use of serum had undoubtedly been of definite aid,. (103). 43

In this country until 1928, a polyvalent serum was not obtain­ able, and the results obtained from the use of the simple perfringens serum were for the most pa.rt unsatisfactory (72). Where the poly­ valent serum has been used, however, the results have been eminently satisfactory (61, 16~ 65).

At the present time several commercial bre.nds are on the market, but it is essential that they contain antibodies against B Welchi, Vibrion Septique, B Oedematiens; the others do not seem to be of such significance (72). The antitoxin should be given in rather massive doses, since the degree of toxemia and local tissue reaction is great. The use of 50,000 to 100,li>OO units is advised

(19). It m~ be given intra-venously or intra-muscularly, as well as applied directly to the wound. As with its prophylactic use, no hard and fast rules mq be laid down governing its use, but ea.ch case must determine this for itself; the important thing seems to be giving the serum in sufficiently large doses.

(3) X-RAY RADIATION

In 1933, J F Kelly reported six cases of gas infection of the extremities treated with the accepted surgical and serologic measures plus the use of small doses of X-ray, all of which re­ covered. He stated at that time that he was at a loss to explain the apparent beneficial results but strongly recommended the fur­ ther investigation of its value by other men (55). This is the 44 recorded instance of the use Of X-rq in the treatment of this

condition, al.tho~ Desjardius, in 1931, had published a review of the use of the X-ra.7 in marq other inflammatory conditions (23). One year later (1934), Faust reviewed 7 cases treated with slightly stronger doses of X-rq with good results. He stated that as a possible explanation of the mode of

He also stated that the X-rq was of marked value in the condition, and should be further investigated (29, 30). In 1936, Xel:l;y again reviewed 40 cases of his own and of

others, in which X-rq ha.cl been used. He stated at this time that the mortality aor the entire series was 8.9%, a marked reduction

from that reported in aD7 series up to that time. As regards

technic, he rec~mmended that the readiation be given merning and evening overi-a period of at lea.st three dqs and of sufficient voltage to insure penetration of the involved tissue: from 90-100 kilovolts on an extremit;y, 1 mm aluminum filter, from 130-160 kilovolts on the trunk with increased filtration; about 100 roentgens per theatment over each area (56, 57). While still comparatively new, this 8.ddition to our armamen- tariwn is rapidly becoming recognized as one of our most effic- ient weapons in combating this infection • • • 45 (4) OXIDIZJNG AGENTS

As stated above, Fraenkel advocated the use of :8202 as long

ago as 1893, just one 7ear after the discovery of the organism by Welch. Since that time man7 investigators have emplo7ed this and other oxidizing agents in the treatment of active gas bacil­ lus infections. 'l'he rationale has been to combat the organisms on a biological basis, in the hope of OXTgenating the tissues and of thus rendering them unsuitable for the growth of anaerobic bacteria. During the World War, Seefisch (94), Bocker (7), and Borchers (10) advised the use of free Oxygen by insufflation as well as by­ direct injection into the infected area.. Borchers, however, stressed

the dangers of air embolism in this procedure, and reported five fatalities because of this complication. J'rom time to time, !Mn04 has also been advanced as a means of attack, working along the same line as the use of Olcy'gen and H202. In general, however, the results seem to have been no better than those obtained with the usual measures (100). Indeed Delbet showed experimentally' that the gas bacillus grew better on muscle tissue previously treated with 11202 than on muscles not so treated (21). Though of auxillary value in the treatment of the disease, it can be said at the present time that no one or combination of these agents can be considered as invaluable in a case of impending or progressing gangrene (72). What the future holds through the l".... , 46 further investigation of their value, can not be foretold at this . time.

(5) NON-SPECIFIC ANTISEPTICS

In the past, practically' every »:nown antiseptic has been advo­ cated in the chemotherapy of this disease. Iodine (7), iodoform, nitrate of silver, hJpochloride of soda (lla), Gentian Violet (6), carbolic acid (48), hypertonic salt solution (48), formalin (74), alcohol (74), Mercurochrome (3), and soap have all been employed. All have been disappointing, either because it was found that when strong enough to be really' bacteriocidal these agents caused death of iissue and so predisposed to spread of the infection, or when

weak enough to be non-inJurious to the tissues they were practica­ lly useless as antibacterial agenst. Thereupon the discontinuous

use of antiseptic soiutions such as Dald.n 1s solution was suggested

but with similarly unsatisfactory results. It was felt that though this solution was useful as a bacteriocide and as a detergent, it was disadvantageous in that, at the same time, it flushed away the protective antibodies and leucocytes. As a result of Taylor's demonstration of the bacteriocidal

effect in vitro of a l~ solution of quinine sulfate on the gas bacillus (100), Pilcher suggested a quinine mixture which was

8lllplo;red by him w1 th considerable satisfaction (Bl), but again ft 4oes not seem to have received general approval. Delbet, because 47 of its positive chemotaxis for leucocytes, recommended a solution of 1.21% magnesium sulfate (21). Phototherapy, heliotherapy, and thermo therapy have all been used but with the same indifferent success. Bohlman, in 1937, reported three cases treated with Sulfanil­ amide. Twenty to sevent7-five grains were given dail7 by mouth. All three cases recovered, and he is quite enthusiastic over the possibilities Ca?. This agent is still too new to have been properly investigated, but needs further stud1' in the treatment

of this oondi ti on.

'· PROGNOSIS The prognosis of any one case of gas gangrene depends largely upon the rapidity with which treatment is instituted. Mortality figures quoted by different investigators have varied rather widely. This is due in part at least to the development of an increasingly more efficacious attack upon the condition, both prophy'lactical.17 and therapeutically, especially during the World War.

Kummel, in 1915, stated that in his war experience, the mortality was around 3~. Be contrasted this figure with what he claimed was the average mortality during times of peace (80-8~). He was not, however, able to satisfactorily explain this (59). Bocker claimed that the war figure should be closer to so% (7), while La.rdennois analyzed 500 cases during 1915-1916 and stated that the mortality was only 15% (60). Gross estimated that treat­ ment should be given early- by pointing out that a delq in begin­ ning treatment of 12 hours would increase the mortality from 11% to 56%. He obtained this impression by studying 3,300 wounded men (43). Otlher figures given from a study of war injuries are Ivens, 10% (48); Gross, 42% (142); Van Beuren, 32% (103); Duval and Vaucher, 16% (2 5); Mairesse, lo% (66). The mortality from this condition was estimated by Zindel to be from 12-5<>% in military practice and from 70-9<>% in civil practice (40). Loehr quotes the Medical Research Committee as having placed the mortality at from 20-50% for the Al.lies and 49 from 30-6o% for the Central Powers (64). As regards studies of civil series, Weintrob and Messeloff

reviewed 85 cases with a mortality of 45.9% occurring before 1927

(110). Manson, after an exhaustive search, stated (1932) that

the average mortality in American Civil practice was around ~ (68). Millar, in 1932; reviewed 607 cases occurring after 1883. These constituted all of the cases that he could obtain from a

study of the literature, and, of course, represented all forms of

treatment. Of this entire series, 50.~ died. Be also. states that the American Expeditionary Force in France had a death rate

according t.o the Surgeon General's Office of 48.5%, and that the official British Expeditionary Force report gives a mortality

of 20-~ (73). Stone and Holsinger, in 1934, reviewed 67 cases occurring from 1921 to 1933 at the Virginia State Hospital with a mortality of 32.4% (99). ·Kelly,. reporting his series treated with the aid of X-rq, gives a mortality of a.9%, an amazingly low figure. ~Co W1-). :BIBLIG>GRAPHY (1) Albrecht, A - The treatment of Gaseous Gangrene - Beil lflin Wchnschr - 29:940-1916-Abstracted in International Abstract of Surgery - 24:520 - 1917

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